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Biomedical subjects

R Y Yukhananov

Publications and source records attributed to R Y Yukhananov.

8 recordsLinked to original sources
PubMed2002

HSP90 inhibitors alter capsaicin- and ATP-induced currents in rat dorsal root ganglion neurons.

Heat shock proteins (HSPs) are major components of eukaryotic and prokaryotic cells with particularly high levels of expression in neurons. HSPs control protein folding, transport of proteins to and from the nucleus, incorporation of proteins into the cell membrane, and maintenance of the functional activity of several proteins involved in transcriptional control. In this study we demonstrate that inhibitors of HSP90 alter currents mediated by the ligand gated channels, P2X and VR1. P2X and VR1 are membrane receptors activated by ATP and capsaicin, respectively, and are thought to be involved in inflammation-related nociception. The HSP90 inhibitors geldanamycin (GLD), radicicol (RAD) herbimycin A (HERB) potentiated ATP induced currents, whereas only GLD altered capsaicin-induced currents in isolated DRG neurons. At low (< 1 microM) concentrations, GLD potentiated the capsaicin-induced current, while at high concentrations (10-25 microM) it inhibited it. The results suggest a potential involvement of HSPs in nociception.

Adenosine Triphosphate↗
PubMed2001

Gene expression following acute morphine administration.

The long-term response to neurotropic drugs depends on drug-induced neuroplasticity and underlying changes in gene expression. However, alterations in neuronal gene expression can be observed even following single injection. To investigate the extent of these changes, gene expression in the medial striatum and lumbar part of the spinal cord was monitored by cDNA microarray following single injection of morphine. Using robust and resistant linear regression (MM-estimator) with simultaneous prediction confidence intervals, we detected differentially expressed genes. By combining the results with cluster analysis, we have found that a single morphine injection alters expression of two major groups of genes, for proteins involved in mitochondrial respiration and for cytoskeleton-related proteins. RNAs for these proteins were mostly downregulated both in the medial striatum and in lumbar part of the spinal cord. These transitory changes were prevented by coadministration of the opioid antagonist naloxone. Data indicate that microarray analysis by itself is useful in describing the effect of well-known substances on the nervous system and provides sufficient information to propose a potentially novel pathway mediating its activity.

Analgesics, Opioid↗
PubMed1997

Estrogen alters proenkephalin RNAs in the paraventricular nucleus of the hypothalamus following stress.

Gonadal steroids modulate activity of the hypothalamo-pituitary-adrenal axis (HPA) following stress, but the regulatory pathways of this modulation are unknown. A possible site of action is the synthesis of CRH and/or enkephalin in cells of the paraventricular nucleus of the hypothalamus (PVN). To investigate this possibility, we utilized two stressors, i.p. hypertonic saline injection (HSI) or exposure to novel environment, and examined the response of CRH or c-fos mRNAs and proenkephalin (PPE) mRNA and heteronuclear RNA (hnRNA, primary transcript). Male rats were gonadectomized and treated with estrogen or dihydrotestosterone propionate (DHTP) for 2 weeks. In situ hybridization revealed that novelty or HSI elevated levels of PPE hnRNA and c-fos mRNA in the PVN. Estrogen attenuated the elevation of PPE hnRNA in the PVN following HSI, and enhanced the c-fos mRNA response to novelty. In contrast, DHTP did not affect PPE hnRNA, but inhibited the c-fos mRNA response to novelty. These data indicate that in male rats estrogen receptor but not androgen receptor may modulate the endocrine stress response by altering PPE transcription in the PVN and that this effect depends on the type of stressor.

Animals↗
PubMed1997

Bifurcation model of drug dependence.

Chronic administration of narcotics produces alterations which persist for a long time following cessation of drug usage in a state of abstinence. The current model of drug dependence which is based on the narcotic-induced alterations of adenylatecyclase synthesis and activity cannot explain these long-term changes. The possible modification of this model suitable to explain the state of abstinence, is described. The modified model consists of two non-linear differential equations describing the dynamics of enzyme synthesis and enzyme-product interaction. Under certain conditions narcotics interconvert the regulatory system from 'normal' equilibrium to an 'abstinent' state in which the system can remain indefinitely, even in the absence of narcotics.

Animals↗
PubMed1997

Effect of morphine on proenkephalin gene expression in the rat brain.

Previous studies indicate that an acute injection of morphine does not effect the level of opioid peptides and their mRNA in the brain. However, due to the presence of a large pool of mRNA and possible opposing changes in turnover rate it is often difficult to visualize the transitory and relatively small alterations in gene transcription by examining mRNA level. Therefore, in situ hybridization with probes directed against intronic sequences to measure the primary transcript of proenkephalin (PPE) mRNA (heteronucleic RNA, hnRNA) in the rat brain following morphine administration was used in this study. The distribution of the hybridization signal of probes against both the A and B intron of the PPE gene were identical and coincide with the distribution PPE mRNA. Thus, to increase the sensitivity of this assay both probes were concurrently hybridized. Female and male Sprague-Dawley rats were gonadectomized and injected with morphine (10 mg/kg, SC). We detected no changes in PPE mRNA levels in the striatum, olfactory tubercle (OT) and n. accumbens core (NAC) at any time following morphine administration. However, from 0.5 h until 24 h following morphine injection, the levels of PPE hnRNA in NAC and OT but not in the dorsal striatum were significantly decreased. The level of c-fos mRNA was increased only the dorsal striatum following morphine injections. These data show that morphine administration can acutely change opioid peptide gene transcription. The observed decrease of PPE hnRNA levels for 24 h following a single morphine injection may indicate its importance for the development of acute and chronic dependence. However, the significance of these alterations in PPE gene transcription in term of the acute effect of morphine is not clear, because the steady-state level of mRNA was not changed.

Animals↗
PubMed1996

Alterations in kappa opioid receptor mRNA levels in the paraventricular nucleus of the hypothalamus by stress and sex steroids.

In this study, the levels of kappa opioid receptor (kOR) mRNA were determined using in situ hybridization following two types of stress (i.p. injection of hypertonic saline or novelty). In addition, we examined the possibility that estrogen or androgen would modify kOR mRNA. Gonadectomized male rats treated with estrogen or dihydrotestosterone were sacrificed 45 min after spending 15 min in a novel open field, or 60 min following hypertonic saline injection. Two-way ANOVA revealed that estrogen and novelty increased the levels of kOR mRNA in the ventral zone of the medial parvocellular part of the paraventricular nucleus (PVN), but not in the lateral parvocellular part of the PVN, claustrum, nucleus accumbens or the nucleus of the lateral olfactory tract. Furthermore, novelty increased kOR mRNA in gonadectomized (GDX) and GDX rats treated with dihydrotestosterone (DHTP), but not in sham-operated or estrogen-treated animals. Taken together, these data indicate that kOR mRNA levels are under estrogenic control and up-regulated in a stressor specific fashion.

Animals↗
PubMed1992

Ethanol and delta-sleep-inducing peptide: effects on brain monoamines.

The brain content of dopamine (DA) and its metabolites [dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] were the same in rats with different immobilization times in forced swimming test, while the serotonin (5-HT) concentration was higher in high active (HA, immobilization < 2 min) than low active (LA, immobilization > 5 min) animals. Ethanol (2 g/kg, PO) tended to increase the DA level in the striatum and nucleus accumbens in LA rats and decrease the 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) concentration in HA rats. delta-Sleep-inducing peptide (DSIP) injection reduced the level of 5-HT in the medial prefrontal cortex (MFC) in both groups, did not affect the concentration of DA or DOPAC, but increased HVA in the striatum of HA rats. DSIP injected before ethanol administration augmented the ethanol effects on 5-HT in the MFC and attenuated the action of ethanol on 5-HIAA in the nucleus accumbens. A relationship between the different levels of voluntary alcohol consumption and sensitivity to stress among LA and HA rats and the differences in DA and 5-HT concentrations is suggested. The use of LA and HA rats in developing models for testing of stress-shielding compounds is also described.

3,4-Dihydroxyphenylacetic Acid↗